Vancomycin Pharmacokinetics in Patients on Peritoneal Dialysis

• Sponsor: Thomas Jefferson University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03685747
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arm: 1
• Actual Duration (Months): 22.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Vancomycin is the most commonly used empiric treatment for infectious peritonitis in patients on peritoneal dialysis. Current dosing and monitoring for safety and efficacy is empiric, especially for those on rapid-cycling modalities. The goal of this study is to understand the pharmacokinetics of vancomycin in patients on rapid-cycling peritoneal dialysis modalities in order to derive an optimal dosing regimen.

Condition or Disease	Intervention/Treatment	Phase
Peritoneal Dialysis-associated Peritonitis	Drug: Vancomycin	Phase 1

Detailed Description

Peritoneal dialysis (PD) is a form of renal replacement therapy indicated for those with acute kidney injury or end stage renal disease. Currently, two modalities of PD exist and is individualized based on patient and life-style specific factors. Continuous ambulatory peritoneal dialysis (CAPD) allows 4 - 5 exchanges performed manually whereas automated peritoneal dialysis (APD) involves continuous, automated, cyclical exchanges performed by a device at home during the night. Peritonitis is a common complication in PD and accounts for a large portion of hospital readmission and mortality. Vancomycin is the most common antibiotic recommended and has notable gram-positive coverage used empirically during suspected peritonitis.

Despite widespread use, vancomycin lacks good pharmacokinetic characterization in PD. Early pharmacokinetic studies using vancomycin were conducted predominantly in patients on CAPD on glucose-based prescriptions. Data is non-existent in PD patients administered the novel dialysate solution icodextrin, or those treated with overnight APD. The impact of residual kidney function (RKF) on vancomycin in PD is also lacking. Enhanced vancomycin clearance in RKF may result in under-dosing, while overdosing may result in nephrotoxicity and loss of clinically important RKF.

The investigators will characterize the pharmacokinetic profile of vancomycin following a single intraperitoneal dose of vancomycin in icodextrin dialysate to non-infected PD patients and examine the relationship between RKF and vancomycin clearance using serum, dialysate and urine. The goal is to use this data in non-infected subjects to generate information to guide vancomycin dosing in patients on rapid-cycling PD modalities.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Prospective, Single-site, Open-label, Pharmacokinetic Study of Intermittent Intraperitoneal Vancomycin in Adult Subjects Receiving Automated Peritoneal Dialysis
• Actual Study Start Date: Nov 15, 2018
• Actual Primary Completion Date: Aug 30, 2020
• Actual Study Completion Date: Oct 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vancomycin A single 20 mg/kg intraperitoneal dose in 1-liter of 7.5% icodextrin solution of vancomycin will be administered. Sparse blood sampling will be obtained during an overnight 12-hour dwell and during the exchange period.	Drug: Vancomycin; Vancomycin one-time 20 mg/kg intraperitoneal dose.

Outcome Measures

Primary Outcome Measures

1. Maximum Total Plasma Concentration (Cmax) [Day: 1]

   Total systemic plasma concentration following 12-hour dwell

2. Time to Maximum Plasma Concentration (Tmax) [Day: 1]

   Time (hours) to achieve the maximum plasma concentration

3. Area Under the Concentration-time Curve (AUC0-inf) [Days: 1-7]

   AUC based on vancomycin plasma concentrations

4. Total Body Clearance (CLtotal) [Days: 1-7]

   Total vancomycin plasma vancomycin clearance

5. Dialytic Clearance [Days: 1-7]

   Vancomycin clearance from peritoneal dialysis

Secondary Outcome Measures

1. Adverse Events [Days: 1-7]

   Any adverse events throughout entirety of study as assessed by physician-investigator

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult male or females between 18 - 85 years old

• Stabilized on a PD regimen for > 3 months prior to study initiation

Exclusion Criteria:

• Clinically significant disease unrelated to renal impairment or deemed unfit by the investigator

• Allergy or hypersensitivity to vancomycin or icodextrin-containing dialysis solution

• Active peritonitis infection

• Previous intraperitoneal antibiotic treatment within 2 months

• Previous intravenous vancomycin treatment within 2 months

• Hemoglobin < 9 g/dL

• Pregnant or breast-feeding women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107

Sponsors and Collaborators

• Thomas Jefferson University

Investigators

• Principal Investigator: Walter K Kraft, MD, Thomas Jefferson University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 15, 2019

More Information

Publications

None provided.

• Responsible Party: Walter K. Kraft, Clinical Research Unit Medical Director, Thomas Jefferson University
• ClinicalTrials.gov Identifier: NCT03685747
• Other Study ID Numbers: 12451
• First Posted: Sep 26, 2018
• Last Update Posted: Mar 3, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Walter K. Kraft, Clinical Research Unit Medical Director, Thomas Jefferson University: Vancomycin; Pharmacokinetics; Pharmacodynamics; Automated Peritoneal Dialysis
• Additional relevant MeSH terms: Peritonitis; Vancomycin

Study Results

Participant Flow

Arm/Group Title	Vancomycin
Arm/Group Description	A single 20 mg/kg intraperitoneal dose in 1-liter of 7.5% icodextrin solution of vancomycin will be administered. Sparse blood sampling will be obtained during an overnight 12-hour dwell and during the exchange period. Vancomycin: Vancomycin one-time 20 mg/kg intraperitoneal dose.
Period Title: Overall Study
STARTED	4
COMPLETED	4
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Vancomycin
Arm/Group Description	A single 20 mg/kg intraperitoneal dose in 1-liter of 7.5% icodextrin solution of vancomycin will be administered. Sparse blood sampling will be obtained during an overnight 12-hour dwell and during the exchange period. Vancomycin: Vancomycin one-time 20 mg/kg intraperitoneal dose.
Overall Participants	4
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	3 75%
>=65 years	1 25%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43 (19)
Sex: Female, Male (Count of Participants)
Female	1 25%
Male	3 75%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 75%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 25%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	4 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Total Plasma Concentration (Cmax)
Description	Total systemic plasma concentration following 12-hour dwell
Time Frame	Day: 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vancomycin
Arm/Group Description	A single 20 mg/kg intraperitoneal dose in 1-liter of 7.5% icodextrin solution of vancomycin will be administered. Sparse blood sampling will be obtained during an overnight 12-hour dwell and during the exchange period. Vancomycin: Vancomycin one-time 20 mg/kg intraperitoneal dose.
Measure Participants	4
Mean (Standard Deviation) [mg/L]	28.7 (4.9)

2. Primary Outcome

Title	Time to Maximum Plasma Concentration (Tmax)
Description	Time (hours) to achieve the maximum plasma concentration
Time Frame	Day: 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vancomycin
Arm/Group Description	A single 20 mg/kg intraperitoneal dose in 1-liter of 7.5% icodextrin solution of vancomycin will be administered. Sparse blood sampling will be obtained during an overnight 12-hour dwell and during the exchange period. Vancomycin: Vancomycin one-time 20 mg/kg intraperitoneal dose.
Measure Participants	4
Median (Full Range) [hours]	14.4

3. Primary Outcome

Title	Area Under the Concentration-time Curve (AUC0-inf)
Description	AUC based on vancomycin plasma concentrations
Time Frame	Days: 1-7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vancomycin
Arm/Group Description	A single 20 mg/kg intraperitoneal dose in 1-liter of 7.5% icodextrin solution of vancomycin will be administered. Sparse blood sampling will be obtained during an overnight 12-hour dwell and during the exchange period. Vancomycin: Vancomycin one-time 20 mg/kg intraperitoneal dose.
Measure Participants	4
Mean (Standard Deviation) [hr x mg/L]	2589.9 (365.6)

4. Primary Outcome

Title	Total Body Clearance (CLtotal)
Description	Total vancomycin plasma vancomycin clearance
Time Frame	Days: 1-7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vancomycin
Arm/Group Description	A single 20 mg/kg intraperitoneal dose in 1-liter of 7.5% icodextrin solution of vancomycin will be administered. Sparse blood sampling will be obtained during an overnight 12-hour dwell and during the exchange period. Vancomycin: Vancomycin one-time 20 mg/kg intraperitoneal dose.
Measure Participants	4
Mean (Standard Deviation) [mL/min]	7.2 (1.3)

5. Primary Outcome

Title	Dialytic Clearance
Description	Vancomycin clearance from peritoneal dialysis
Time Frame	Days: 1-7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vancomycin
Arm/Group Description	A single 20 mg/kg intraperitoneal dose in 1-liter of 7.5% icodextrin solution of vancomycin will be administered. Sparse blood sampling will be obtained during an overnight 12-hour dwell and during the exchange period. Vancomycin: Vancomycin one-time 20 mg/kg intraperitoneal dose.
Measure Participants	4
Mean (Standard Deviation) [mL/min]	11.1 (4.3)

6. Secondary Outcome

Title	Adverse Events
Description	Any adverse events throughout entirety of study as assessed by physician-investigator
Time Frame	Days: 1-7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vancomycin
Arm/Group Description	A single 20 mg/kg intraperitoneal dose in 1-liter of 7.5% icodextrin solution of vancomycin will be administered. Sparse blood sampling will be obtained during an overnight 12-hour dwell and during the exchange period. Vancomycin: Vancomycin one-time 20 mg/kg intraperitoneal dose.
Measure Participants	4
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	10 days
Adverse Event Reporting Description	Subjects were assessed daily for adverse events till day 7 and then again on day 10 post study visit
Arm/Group Title	Vancomycin
Arm/Group Description	A single 20 mg/kg intraperitoneal dose in 1-liter of 7.5% icodextrin solution of vancomycin will be administered. Sparse blood sampling will be obtained during an overnight 12-hour dwell and during the exchange period. Vancomycin: Vancomycin one-time 20 mg/kg intraperitoneal dose.
All Cause Mortality
	Vancomycin
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Serious Adverse Events
	Vancomycin
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	Vancomycin
	Affected / at Risk (%)	# Events
Total	0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.